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ArticleClinical research in cardiology : official journal of the German Cardiac Society2026

Continuously elevated plasma ketone bodies are linked to adverse outcomes in patients with heart failure.

Constantin L Palm, Niels T B Scholte, Lirong Lu, Sabrina Abou Kamar, Barbara M Bakker, Suzanne N Voorrips, Belend Mahmoud, Margery A Connelly, Navin Suthahar, Rudolf A de Boer and 6 more

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Article in Clinical research in cardiology : official journal of the German Cardiac Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

16 authors.

Constantin L Palm *Department of Cardiology, University of Groningen, Groningen University Medical Center, HPC AB31, Postbox 30.001, 9700 RB, Groningen, The Netherlands.ORCID http://orcid.org/0009-0006-6044-1299
Niels T B Scholte *Department of Cardiology, Cardiovascular Institute, Erasmus, MC, 3000 CA, Rotterdam, The Netherlands.
Lirong LuDepartment of Cardiology, Cardiovascular Institute, Erasmus, MC, 3000 CA, Rotterdam, The Netherlands.
Sabrina Abou KamarDepartment of Cardiology, Cardiovascular Institute, Erasmus, MC, 3000 CA, Rotterdam, The Netherlands.
Barbara M BakkerLaboratory of Pediatrics, Department of Pediatrics, University of Groningen, Groningen University Medical Center, Groningen, The Netherlands.
Suzanne N VoorripsDepartment of Cardiology, University of Groningen, Groningen University Medical Center, HPC AB31, Postbox 30.001, 9700 RB, Groningen, The Netherlands.
Belend MahmoudDepartment of Cardiology, University of Groningen, Groningen University Medical Center, HPC AB31, Postbox 30.001, 9700 RB, Groningen, The Netherlands.
Margery A ConnellyDiagnostics R & D, Labcorp, Morrisville, USA.
Navin SuthaharDepartment of Cardiology, Cardiovascular Institute, Erasmus, MC, 3000 CA, Rotterdam, The Netherlands.
Rudolf A de BoerDepartment of Cardiology, Cardiovascular Institute, Erasmus, MC, 3000 CA, Rotterdam, The Netherlands.
Victor A UmansDepartment of Cardiology, Noordwest Ziekenhuisgroep Alkmaar, The Netherlands.
K Martijn AkkerhuisDepartment of Cardiology, Cardiovascular Institute, Erasmus, MC, 3000 CA, Rotterdam, The Netherlands.
Hans HillegeDepartment of Cardiology, University of Groningen, Groningen University Medical Center, HPC AB31, Postbox 30.001, 9700 RB, Groningen, The Netherlands.
Eric BoersmaDepartment of Cardiology, Cardiovascular Institute, Erasmus, MC, 3000 CA, Rotterdam, The Netherlands.
Isabella Kardys *Department of Cardiology, Cardiovascular Institute, Erasmus, MC, 3000 CA, Rotterdam, The Netherlands.
B Daan Westenbrink *Department of Cardiology, University of Groningen, Groningen University Medical Center, HPC AB31, Postbox 30.001, 9700 RB, Groningen, The Netherlands. b.d.westenbrink@umcg.nl.

Funding

Center for Translational Molecular Medicine grant 01C-103
6 · The paper itself

Abstract

backgroundElevated plasma ketone bodies (KBs) are linked to poor outcomes in heart failure (HF), yet the prognostic value of repeated KB measurements is uncertain.

objectiveTo study temporal changes in plasma KBs in HF patients in relation to prognosis.

methodsPlasma KBs were measured by nuclear magnetic resonance spectroscopy in 467 patients from the TRIUMPH study. Blood was obtained up to seven times during 1-year follow-up after HF hospitalization. Associations between serial KB measurements and the endpoint of death and HF rehospitalization were investigated by joint modeling. Similar analyses were conducted in the Bio-SHiFT study, including 397 chronic HF patients with up to 10 repeated blood samples during a median follow-up of 2.1 years. The endpoint in Bio-SHiFT was a composite of cardiovascular death, HF hospitalization, left ventricular device implantation and heart transplantation.

resultsIn TRIUMPH, median age was 74 years, 37% of patients were female and 82% were in NYHA class III/IV. Estimated KBs were continuously higher in the 185 (40%) patients reaching the combined endpoint. Hazard ratios (HR) (95% confidence interval [CI]) for the endpoint per doubling of total KBs (TKBs), acetone, and β-hydroxybutyrate were 2.10 (1.27-3.71), 1.62 (1.08-2.44) and 1.62 (1.22-2.23), respectively, at any time during follow-up after adjustment for clinical characteristics and NT-proBNP at baseline. In Bio-SHiFT, median age was 64 years, 28.5% of patients were female, and 124 (31.2%) patients reached the primary endpoint. KBs were higher in patients reaching the endpoint. The HR per doubling of TKB was 5.36 (95% CI 2.18-14.0) and 4.24 (31.4-5.95) for acetone.

conclusionSerially measured KB levels were associated with adverse events in two independent HF cohorts. Patients with adverse events displayed consistently higher KBs, potentially reflecting ongoing metabolic stress.

Indexed as

Joint modelKetone body metabolismMetabolic stressRisk stratification

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.